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Metabolism and degradation kinetics of selected veterinary drugs in manure.

Prof Dr. M. Spiteller, Universität Dortmund


The fate and metabolism of the veterinary drugs sulfadiazine (SDZ) and difloxacin (DIF) was studied after application to fattening pigs by means of newly developed, robust, specific and sensitive analytical LC-MS/MS methods for the quantitation of the applied drugs and their biotransformed metabolites in manure, soil/manure and plants. New transformation products could be identified unambiguously by high resolution mass spectrometry. Knowledge about the metabolite pattern in manure is a prerequisite for risk assessment, as the manure may be spread into the environment. The use of 14C-labelled compounds allowed a complete mass balance of the applied drug and its metabolites after administration to fattening pigs. In the case of SDZ, the analysis of manure revealed two known metabolites, N-acetylsulfadiazine (Ac-SDZ) and 4-hydroxysulfadiazine (4-OH-SDZ), and two hitherto unidentified minor metabolites (N-formylsulfadiazine and N-acetyl-4-hydroxysulfadiazine). While from the excreted radioactivity SDZ accounted for 44%, more than 50% were biotransformation products. The analysis of manure after treating pigs with DIF showed that 90% of DIF was excreted as parent compound. The residual radioactivity contained the bioactive main metabolite Sarafloxacin (10%) and three trace metabolites (<1%). Storage of manure is routine step prior further proceeding in agricultural practice. During the storage (SDZ application) under aerobic and anaerobic conditions, the concentration of SDZ increased due to deacetylation of Ac-SDZ, 4-OH-SDZ concentrations remained constant. Storage of manure after DIF application exhibited no significant transformation or degradation of DIF. Sorption of organic compounds to soil form bound residues or so called non extractable residues (NER). Thus, leaching into groundwater may be avoided and bioavailability is limited. A rapid formation of non-extractable residues could be observed for both antibiotics. Sorption of DIF was fast, very strong and dominated by anionic species. The concentration of extractable SDZ and its metabolites in soil decreased exponentially, Surprisingly Ac-SDZ is directly converted into bound residues via fast process and not converted to SDZ. A significant amount of SDZ was found tightly bound to soil particles and did not desorb. The covalent binding of SDZ to soil humic substances occur via the free amino group as concluded from 15N-NMR experiments. The presence of manure enhanced the hysteresis effect observed and sorption tendency increased significantly. Thus, in fate studies of environmental contaminants the influence of manure should not be underestimated. Photolysis is a major degradation/transformation process in the environment. In aqueous solution and manure SDZ revealed the formation of five known photoproducts and one new compound. The extrusion of the functional SO2 group was found to be the main degradation process. During prolonged photo-degradation of DIF, seven photoproducts were identified, three of which were entirely novel. Residual anti-bacterial activities of DIF, sarafloxacin and also their photoproducts against a group of pathogenic strains were measured with varying degrees of efficacies against the tested bacteria. The plant uptake of SDZ and DIF was studied with maize. Less than 1.5 % (0.2% for DIF) of the applied radioactivity could be detected in the plants. Under the influence of roots a 10 time’s higher mineralization of SDZ and formation of about 3 times less non-extractable residues was observed. Furthermore, the abundance and transferability of bacterial antibiotic resistance genes were most pronounced in the vicinity of roots under conditions of maximum SDZ transformation. Variation of soil moisture (drying, re-wetting) and temperature conditions exhibited no significant influence on the fate of SDZ in soil.



begutachtete Publikationen:

  1. Lamshöft, M, Sukul, P, Zühlke, S, Spiteller, M (2007): Metabolism of 14C-labelled and non- labelled Sulfadiazine after administration to pigs. Analytical and Bioanalytical Chemistry 388, 1733¬–1757.
  2. Heuer, H, Focks, A, Lamshöft, M, Matthies, M, Spiteller, M (2008): Fate of sulfadiazine administered to pigs and its quantitative effect on the dynamics of bacterial resistance genes in manure and manured soil. Soil Biology & Biochemistry 40, 1892–1900.
  3. Sukul, P, Lamshöft, M, Zühlke, S, Spiteller, M (2008): Photolysis of 14C-sulfadiazine in water and manure Chemosphere 71, 717–725.
  4. Sukul, P, Lamshöft, M, Zühlke,S, Spiteller, M (2008): Sorption and desorption of sulfadiazine in soil and soil-manure systems. Chemosphere 73, 1344–1350.
  5. Sukul, P, Lamshöft, M, Kusari, S, Zühlke, S, Spiteller, M (2009): Metabolism and excretion kinetics of 14C-labeled and non-labeled difloxacin in pigs after oral administration, and antimicrobial activity of manure containing difloxacin and its metabolites. Environmental Research 109, 225–231.
  6. Deivasigamani, P, Sukul, P, Lamshöft, M, Mohan, A, Zühlke, S, Spiteller, M (2009): Photolysis of Difloxacin and Sarafloxacin in Aqueous Systems. Chemosphere 77, 739–746.
  7. Sukul, P, Lamshöft, M, Kusari, S, Zühlke, S, Spiteller, M (2009): Metabolism and excretion kinetics of 14C-labeled and non-labeled difloxacin in pigs after oral administration, and antimicrobial activity of manure containing difloxacin and its metabolites. Environmental Research 109, 225–231.
  8. Kusari, S, Deivasigamani, P, Lamshöft, M, Spiteller, M (2009): In Vitro Residual Anti-bacterial Activity of Difloxacin, Sarafloxacin and their Photoproducts after Photolysis in Water. Environmental Pollution 157, 2722–2730.
  9. Lamshöft, M, Sukul, P, Zühlke, S, Spiteller, M (2010): Behavior of 14C-sulfadiazine and 14C-difloxacin during manure storage. Science of the  Total Environment 408, 1563–1568.
  10. Kotzerke, A, Hammesfahr, U, Kleineidam, K, Lamshöft, M, Thiele-Bruhn, S, Schloter, M, Wilke, B.-M (2010): Influence of difloxacin-contaminated manure on microbial community structure and function in soils. Biology and Fertility of Soils 47, 177–186.
  11. Hammesfahr, U, Kotzerke, A, Lamshöft, M, Wilke, B.-M, Kandeler, E, Thiele-Bruhn S (2011): Effects of sulfadiazine-contaminated fresh and stored manure on a soil microbial community. European Journal of Soil Biology, 47 61–68.
  12. Rosendahl. I, Siemens. J, Kindler. R, Groeneweg. J, Zimmermann. J, Czerwinski, S, Lamshöft, M, Laabs. V, Wilke. B.M, Vereecken, H, Amelung. W (2012): Persistence of the fluoroquinolone antibiotic difloxacin in soil and lacking effects on N-turnover. Journal of Environmental Quality, 41 1275–1283.